A novel role of CPEB3 in regulating EGFR gene transcription via association with Stat5b in neurons.

Nucleic Acids Research
Shu-Chun PengYi-Shuian Huang

Abstract

CPEB3 is a sequence-specific RNA-binding protein and represses translation of its target mRNAs in neurons. Here, we have identified a novel function of CPEB3 as to interact with Stat5b and inhibit its transcription activity in the nucleus without disrupting dimerization, DNA binding and nuclear localization of Stat5b. Moreover, CPEB3 is a nucleocytoplasm-shuttling protein with predominant residence in the cytoplasm; whereas activation of NMDA receptors accumulates CPEB3 in the nucleus. Using the knockdown approach, we have found the receptor tyrosine kinase, EGFR, is a target gene transcriptionally activated by Stat5b and downregulated by CPEB3 in neurons. The increased EGFR expression in CPEB3 knockdown neurons, when stimulated with EGF, alters the kinetics of downstream signaling. Taken together, CPEB3 has a novel function in the nucleus as to suppress Stat5b-dependent EGFR gene transcription. Consequently, EGFR signaling is negatively regulated by CPEB3 in neurons.

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Citations

Jun 26, 2012·Nucleic Acids Research·Hsu-Wen ChaoYi-Shuian Huang
May 29, 2014·The Journal of Clinical Investigation·Roberto FerrareseMarkus Bredel
May 1, 2012·Ageing Research Reviews·Gonzalo Fernández-Miranda, Raúl Méndez
Dec 14, 2011·The EMBO Journal·Po-Jen Chen, Yi-Shuian Huang
Jun 14, 2012·PloS One·Tillmann WeberDusan Bartsch
Jun 1, 2018·Oxidative Medicine and Cellular Longevity·Nikolai EngedalMaria Cristina Albertini
Sep 28, 2017·Nature Communications·Lifang LiLuyang Sun
Aug 21, 2014·Circulation. Cardiovascular Genetics·Mario FloresYufei Huang

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Methods Mentioned

BETA
SELEX
two-hybrid
nuclear translocation
PCR
Co-immunoprecipitation
immunoprecipitation
ChIP
transfection
two hybrid
immunoprecipitation assay

Software Mentioned

MATCH
TrackMot

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